Trimetrexate-leucovorin dosage evaluation study for treatment of Pneumocystis carinii pneumonia

Pneumocystis carinii (Pc) pneumonia occurs in more than 80 percent of AIDS cases, and is one of the primary causes of death in patients with AIDS. The current therapy for Pc pneumonia consists of trimethoprim-sulfamethoxazole (T-S) or pentamidine isethionate (P-I), and produces significantly adverse side effects in as many as 80 percent of patients. Nonetheless, Pc pneumonia mortality ranges between 40 and 60 percent of cases. Trimetrexate (TX) is a new agent with promising effects. Its mode of action is the same as T-S, but it is 1,500 times more effective in binding to dihydrofolate reductase of pneumocystis. The addition of leucovorin (5-formyl tetrahydrofolate; LV) protects the patient's cells from the cytotoxic effects of TX. Used together, TX-LV should be a significant adjunct to the current formulary of AIDS patients with Pc pneumonia. A group of 54 AIDS patients with Pc pneumonia were enrolled in a dosage evaluation trial with TX-LV. Varying dosage schedules and combinations were administered, and the side effects, particularly hematologic (blood-related) in nature, were assessed. A full treatment course consisted of 21 full doses of TX. Therapeutically effective combination doses were achieved at 45 milligrams per square meter per day of TX and 80 milligrams per square meter per day of LV. Further control studies are recommended to compare the safety and effectiveness of these drugs with other medications used to treat Pc pneumonia. (Consumer Summary produced by Reliance Medical Information, Inc.)